Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (688 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Phase of the cell cycle following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Phase, S; Phases, S; S Phases; S Period; Period, S; Periods, S; S Periods.
Where it fits in the MeSH classification
- Broader topics
- DNA Replication; Interphase
- Narrower topics
- S Phase Cell Cycle Checkpoints
- See also
- DNA Replication; DNA Replication Timing
Related concepts
Research landscape
PubMed indexes 10,897 records tagged with the MeSH heading “S Phase” (counts retrieved 2026-10-29). 616 of them (5.7%) were published from 2020 onward, and the busiest period so far is 2000-2009 with 4,027 records.
Reviews account for 569 records (5.2%) and meta-analyses for 1. Randomized controlled trials number 32 (0.3%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 3,267 |
| 2000-2009 | 4,027 |
| 2010-2019 | 2,987 |
| 2020 onward | 616 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 569 | 5.2% |
| Meta-analyses | 1 | 0.0% |
| Randomized controlled trials | 32 | 0.3% |
Method: PubMed query "S Phase"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in molecular biology
Molecular biology establishes mechanisms through controlled experiments, often in simplified systems such as purified proteins, cultured cells or model organisms. Such work can show what is possible in a defined system, but whether a pathway matters in a whole organism or in human disease needs further evidence. Check the experimental system, whether findings were reproduced by independent groups, and whether the authors tested the mechanism directly or inferred it from correlation.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| DNA damage during S-phase mediates the proliferation-quiescence decision in the subsequent G1 via p21 expression | 2017 | Research article Design not recorded in structured metadata | 355 | cc by PMID 28317845 · DOI · PMC5364389 |
| Genetic instability from a single S phase after whole-genome duplication | 2022 | Research article Design not recorded in structured metadata | 130 | cc by PMID 35355016 · DOI · PMC8986533 |
| β-Thujaplicin induces autophagic cell death, apoptosis, and cell cycle arrest through ROS-mediated Akt and p38/ERK MAPK signaling in human hepatocellular carcinoma | 2019 | Research article Design not recorded in structured metadata | 120 | cc by PMID 30874538 · DOI · PMC6420571 |
| Nuclear compartmentalization at the G1/S transition plays a key role in DNA replication control | 2026 | Research article Design not recorded in structured metadata | 2 | cc by PMID 42575893 · DOI · PMC13458202 |
DNA damage during S-phase mediates the proliferation-quiescence decision in the subsequent G1 via p21 expression [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Following DNA damage caused by exogenous sources, such as ionizing radiation, the tumour suppressor p53 mediates cell cycle arrest via expression of the CDK inhibitor, p21.
- Closing excerpt
- Thus, we characterize how p21 regulates the proliferation-quiescence decision to maintain genomic stability.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (149 words)
Following DNA damage caused by exogenous sources, such as ionizing radiation, the tumour suppressor p53 mediates cell cycle arrest via expression of the CDK inhibitor, p21. However, the role of p21 in maintaining genomic stability in the absence of exogenous DNA-damaging agents is unclear. Here, using live single-cell measurements of p21 protein in proliferating cultures, we show that naturally occurring DNA damage incurred over S-phase causes p53-dependent accumulation of p21 during mother G2- and daughter G1-phases. High p21 levels mediate G1 arrest via CDK inhibition, yet lower levels have no impact on G1 progression, and the ubiquitin ligases CRL4Cdt2 and SCFSkp2 couple to degrade p21 prior to the G1/S transition. Mathematical modelling reveals that a bistable switch, created by CRL4Cdt2, promotes irreversible S-phase entry by keeping p21 levels low, preventing premature S-phase exit upon DNA damage. Thus, we characterize how p21 regulates the proliferation-quiescence decision to maintain genomic stability.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 28317845 · DOI · PMC5364389
Genetic instability from a single S phase after whole-genome duplication [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Diploid and stable karyotypes are associated with health and fitness in animals.
- Closing excerpt
- These findings provide an explanation for the genetic instability landscape that favours tumorigenesis after tetraploidization.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (172 words)
Diploid and stable karyotypes are associated with health and fitness in animals. By contrast, whole-genome duplications-doublings of the entire complement of chromosomes-are linked to genetic instability and frequently found in human cancers1-3. It has been established that whole-genome duplications fuel chromosome instability through abnormal mitosis4-8; however, the immediate consequences of tetraploidy in the first interphase are not known. This is a key question because single whole-genome duplication events such as cytokinesis failure can promote tumorigenesis9. Here we find that human cells undergo high rates of DNA damage during DNA replication in the first S phase following induction of tetraploidy. Using DNA combing and single-cell sequencing, we show that DNA replication dynamics is perturbed, generating under- and over-replicated regions. Mechanistically, we find that these defects result from a shortage of proteins during the G1/S transition, which impairs the fidelity of DNA replication. This work shows that within a single interphase, unscheduled tetraploid cells can acquire highly abnormal karyotypes. These findings provide an explanation for the genetic instability landscape that favours tumorigenesis after tetraploidization.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 35355016 · DOI · PMC8986533
β-Thujaplicin induces autophagic cell death, apoptosis, and cell cycle arrest through ROS-mediated Akt and p38/ERK MAPK signaling in human hepatocellular carcinoma [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Hepatocellular carcinoma (HCC), a common liver malignancy worldwide, has high morbidity and mortality.
- Closing excerpt
- Taken together these findings suggest that β-Thujaplicin have an ability of anti-HCC cells and may conducively promote the development of novel anti-cancer agents.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (217 words)
Hepatocellular carcinoma (HCC), a common liver malignancy worldwide, has high morbidity and mortality. β-Thujaplicin, a tropolone derivative, has been used in some health-care products and clinical adjuvant drugs, but its use for HCC is unknown. In this study, we found that β-Thujaplicin inhibits the growth of HCC cells, but not normal liver cells, with nanomolar potency. Mechanistically, we found that β-Thujaplicin could induce autophagy, as judged by western blot, confocal microscopy, and transmission electron microscopy. Further using β-Thujaplicin combined with an autophagy blocker or agonist treatment HepG2 cells, we found that β-Thujaplicin induced autophagic cell death (ACD) mediated by ROS caused inhibition of the Akt-mTOR signaling pathway. Moreover, β-Thujaplicin triggered HepG2 apoptosis and increased cleaved PARP1, cleaved caspase-3, and Bax/Bcl-2 ratio, which indicated that β-Thujaplicin induced apoptosis mediated by the mitochondrial-dependent pathway. We also found that increased expression of p21 and decreased expression of CDK7, Cyclin D1, and Cyclin A2 participating in β-Thujaplicin caused the S-phase arrest. It seems that β-Thujaplicin exerts these functions by ROS-mediated p38/ERK MAPK but not by JNK signaling pathway activation. Consistent with in vitro findings, our in vivo study verified that β-Thujaplicin treatment significantly reduced HepG2 tumor xenograft growth. Taken together these findings suggest that β-Thujaplicin have an ability of anti-HCC cells and may conducively promote the development of novel anti-cancer agents.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 30874538 · DOI · PMC6420571
Nuclear compartmentalization at the G1/S transition plays a key role in DNA replication control [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Upon entry into the G1 phase following mitosis, mammalian chromosomal DNA becomes spatially segregated into A and B compartments, which correspond closely to classic euchromatin and heterochromatin, respectively.
- Closing excerpt
- Our findings uncover a previously unrecognized role for GINS4 in regulating nuclear architecture and underscore the biological significance of nuclear compartmentalization in DNA replication control.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (150 words)
Upon entry into the G1 phase following mitosis, mammalian chromosomal DNA becomes spatially segregated into A and B compartments, which correspond closely to classic euchromatin and heterochromatin, respectively. The functional significance of this spatial segregation, however, has remained unexplored due to the lack of means to manipulate this level of chromosomal organization. Through a genome-wide loss-of-function CRISPR screen, we identify GINS4, a component of the replicative DNA helicase complex, as a factor essential for segregation of A and B compartments during the G1-to-S phase transition. Using GINS4 depletion experiments, we show that proper A/B compartment organization at the time of S-phase entry plays a key role in efficient DNA synthesis. Furthermore, DNA synthesis with attenuated A/B compartments is associated with defects in replication timing regulation. Our findings uncover a previously unrecognized role for GINS4 in regulating nuclear architecture and underscore the biological significance of nuclear compartmentalization in DNA replication control.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42575893 · DOI · PMC13458202
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article PCNA, the maestro of the replication fork [5]
- Research article Control of cell cycle transcription during G1 and S phases [6]
- Research article The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition [7]
- Research article Dangers of using "optimal" cutpoints in the evaluation of prognostic factors [8]
- Research article Checking on DNA damage in S phase [9]
- Research article DNA replication origin activation in space and time [10]
References
- Barr AR, Cooper S, Heldt FS, Butera F, Stoy H, Mansfeld J, et al.. DNA damage during S-phase mediates the proliferation-quiescence decision in the subsequent G1 via p21 expression. . 2017. PMID 28317845 · DOI · PMC5364389
- Gemble S, Wardenaar R, Keuper K, Srivastava N, Nano M, Macé AS, et al.. Genetic instability from a single S phase after whole-genome duplication. . 2022. PMID 35355016 · DOI · PMC8986533
- Zhang G, He J, Ye X, Zhu J, Hu X, Shen M, et al.. β-Thujaplicin induces autophagic cell death, apoptosis, and cell cycle arrest through ROS-mediated Akt and p38/ERK MAPK signaling in human hepatocellular carcinoma. . 2019. PMID 30874538 · DOI · PMC6420571
- Oji A, Yusa K, Noda I, Ichinose T, Kondo Y, Hiratani I. Nuclear compartmentalization at the G1/S transition plays a key role in DNA replication control. . 2026. PMID 42575893 · DOI · PMC13458202
- Moldovan GL, Pfander B, Jentsch S. PCNA, the maestro of the replication fork. Cell. 2007. PMID 17512402 · DOI
- Bertoli C, Skotheim JM, de Bruin RA. Control of cell cycle transcription during G1 and S phases. Nat Rev Mol Cell Biol. 2013. PMID 23877564 · DOI · PMC4569015
- Meloche S, Pouysségur J. The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition. Oncogene. 2007. PMID 17496918 · DOI
- Altman DG, Lausen B, Sauerbrei W, Schumacher M. Dangers of using "optimal" cutpoints in the evaluation of prognostic factors. J Natl Cancer Inst. 1994. PMID 8182763 · DOI
- Bartek J, Lukas C, Lukas J. Checking on DNA damage in S phase. Nat Rev Mol Cell Biol. 2004. PMID 15459660 · DOI
- Fragkos M, Ganier O, Coulombe P, Méchali M. DNA replication origin activation in space and time. Nat Rev Mol Cell Biol. 2015. PMID 25999062 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
See how EvidenceLib is built. Spotted an error? Email support@evidencehelix.com.
Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.